A chronic destructive polyarthritis with gross and microscopic features resembling certain of the alterations found in human rheumatoid arthritis follows the intravenous infection of rats with Salmonella enteritidis. Initial observations suggest that the joint disease is mediated by an immune process rather than by local sepsis. A detailed investigation of the Salmonella- associated arthritis (SAA) is proposed to determine whether this readily inducible joint disease in the rat will prove to be a valid and useful model for the experimental study of the pathogenesis of rheumatoid arthritis. Methodology will involve a correlated study employing standard methods of pathology and microbiology to evaluate the role of infection in the development of SAA. This will include the culture of tissues and organs and the use of antibiotics. Attempts will be made to elicit the disease with purified antigens in infected and normal rats. Immunological investgations will include a study of serum protein changes and the detection of cell and tissue- bound antigens by means of immunofluorescence. The role of immune systems will also be assessed in weanling and adult hosts. Thymus deprivation, selective immunosuppressive drugs, and antilymphocytic sera will be employed to study cellular aspects of the mediation of SAA. The possibility of adoptive transfer of SAA with sensitized lymphoid cells will be examined further. The results will be compared with documented alterations of the corresponding aspects of human rheumatoid arthritis.